Estrogen-dependent growth of a rat pituitary tumor involves, but does not require, a high level of vascular endothelial growth factor
Estrogen-dependent growth of a rat pituitary tumor involves, but does not require, a high level of vascular endothelial growth factor
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DOI：
10.1177/153537020222700714
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发表时间：
2002-07-01
影响因子：
3.2
通讯作者：
Wendell, DL
中科院分区：
文献类型：
--
作者：
Cracchiolo, D;Swick, JW;Wendell, DL
用合成雌激素己烯雌酚（DES）对Fischer 344（F344）大鼠进行长期（10周）治疗可增加垂体中血管内皮生长因子（VEGF）的水平。这与F344大鼠垂体大肿瘤的发生同时发生。VEGF在雌激素依赖性垂体瘤生长中的作用也得到了以下事实的支持，即在耐肿瘤性布朗挪威（BN）品系的大鼠中，垂体VEGF水平不因雌激素治疗而增加。然而，在F344和BN的F1杂交大鼠中，即使F1杂交大鼠对雌激素应答确实形成垂体瘤，雌激素治疗也不会增加VEGF。数量性状基因座（QLT）定位显示，雌激素依赖性VEGF表达的控制与Edpm 5 QTL有关，Edpm 5 QTL先前被鉴定为雌激素依赖性垂体瘤生长的QTL。相比之下，QTL Edpm 2 -1和Edpm 9 -2（其已被证明各自对雌激素依赖性垂体质量具有与Edpm 5相似的量级的显著影响）对VEGF水平没有任何影响。两者合计，我们的研究结果支持相关的VEGF表达与雌激素诱导的大鼠垂体瘤的生长，已经由其他人报道，但他们也表明，有显着的生长调节途径，是独立的高水平的VEGF表达。
Long-term (10-week) treatment of Fischer 344 (F344) rats with the synthetic estrogen diethylstilbestrol (DES) increases the level of vascular endothelial growth factor (VEGF) in the pituitary. This is concurrent with the development of a large tumor of the pituitary of F344 rats. A role for VEGF in estrogen-dependent pituitary tumor growth is also supported by the fact that pituitary VEGF level is not increased by estrogen treatment in rats of the tumor-resistant Brown Norway (BN) strain. However, VEGF is not increased by estrogen treatment in an F, hybrid of F344 and BN, even though F, hybrid rats do form pituitary tumors in response to estrogen. Quantitative trait locus (QLT) mapping reveals that control of estrogen-dependent VEGF expression is linked to the Edpm5 QTL, which was previously identified as a QTL for estrogen-dependent pituitary tumor growth. In contrast, the QTL Edpm2-1 and Edpm9-2, which have been shown to each have a significant effect on estrogen-dependent pituitary mass of a magnitude similar to Edpm5, do not have any effect on VEGF level. Taken together, our results support the association of VEGF expression with growth of the estrogen-induced rat pituitary tumor, as has been reported by others, but they also indicate that there is significant pathways of growth regulation that are independent of high-level VEGF expression.